title: Synthesis and SAR of novel benzoxaboroles as a new class of β-lactamase inhibitors.
abstract: A new class of benzoxaborole β-lactamase inhibitors were designed and synthesized. 6-Aryloxy benzoxaborole 22 inhibited AmpC P99 and CMY-2 with K(i) values in the low nanomolar range. Compound 22 restored antibacterial activity of ceftazidime against Enterobacter cloacae P99 expressing AmpC, a class C β-lactamase enzyme. The SAR around the arylbenzoxaboroles, which included the influence of linker and substitutions was also established.
authors.affiliation: Anacor Pharmaceuticals, Inc., 1020 E. Meadow Circle, Palo Alto, CA 94303, USA. axia@anacor.com
authors.forename: Yi
authors.initials: Y
authors.lastname: Xia
authors.forename: Kathy
authors.initials: K
authors.lastname: Cao
authors.forename: Yasheen
authors.initials: Y
authors.lastname: Zhou
authors.forename: M R K
authors.initials: MR
authors.lastname: Alley
authors.forename: Fernando
authors.initials: F
authors.lastname: Rock
authors.forename: Manisha
authors.initials: M
authors.lastname: Mohan
authors.forename: Maliwan
authors.initials: M
authors.lastname: Meewan
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Baker
authors.forename: Sarah
authors.initials: S
authors.lastname: Lux
authors.forename: Charles Z
authors.initials: CZ
authors.lastname: Ding
authors.forename: Guofeng
authors.initials: G
authors.lastname: Jia
authors.forename: Maureen
authors.initials: M
authors.lastname: Kully
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Plattner
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001583:Benzoxazoles / Q000737:chemistry*; D001896:Boron Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D016972:Enterobacter cloacae / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D011719:Pyrazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D001583:Benzoxazoles; D001896:Boron Compounds; D004791:Enzyme Inhibitors; D011719:Pyrazines; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases